Kallapur Suhas G, Nitsos Ilias, Moss Timothy J M, Polglase Graeme R, Pillow J Jane, Cheah Fook-Choe, Kramer Boris W, Newnham John P, Ikegami Machiko, Jobe Alan H
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
Am J Respir Crit Care Med. 2009 May 15;179(10):955-61. doi: 10.1164/rccm.200811-1728OC. Epub 2009 Feb 20.
Chorioamnionitis frequently associates with preterm delivery and increased amniotic fluid IL-1, and causes fetal lung and systemic inflammation. However, chorioamnionitis is also associated with a paradoxical reduction in the incidence of surfactant deficiency-related respiratory distress syndrome in preterm infants.
To identify the role of IL-1 signaling in the mediation of pulmonary and systemic inflammation and lung maturation in a fetal sheep model of lipopolysaccharide (LPS) induced chorioamnionitis.
After confirming the efficacy of recombinant human IL-1 receptor antagonist (rhIL-1ra), fetal sheep were exposed to intraamniotic (IA) injections of Escherichia coli LPS with or without prior IA injections of rhIL-1ra. Preterm lambs were delivered at 82% of term gestation.
rhIL-1ra decreased IA LPS-induced lung inflammation assessed by decreased lung neutrophil and monocyte influx, inducible nitric oxide synthase expression, lung IL-6 and IL-1beta mRNA expression, and airway myeloperoxidase concentrations. rhIL-1ra inhibited IA LPS-induced fetal systemic inflammation assessed by decreased plasma IL-8, protein carbonyls, blood neutrophilia, and the expression of serum amyloid A3 mRNA in the liver. rhIL-1ra also partially blocked the lung maturational effects of IA LPS. Therefore blockade of IL-1 signaling in the amniotic compartment inhibited fetal lung and systemic inflammation and lung maturation in response to LPS-induced chorioamnionitis.
IL-1 plays a central role in the pathogenesis of chorioamnionitis-induced fetal inflammatory responses.
绒毛膜羊膜炎常与早产及羊水白细胞介素-1（IL-1）升高相关，并可导致胎儿肺部及全身炎症。然而，绒毛膜羊膜炎还与早产儿表面活性物质缺乏相关的呼吸窘迫综合征发病率的反常降低有关。
在脂多糖（LPS）诱导的绒毛膜羊膜炎胎儿绵羊模型中，确定IL-1信号在介导肺部及全身炎症和肺成熟中的作用。
在证实重组人IL-1受体拮抗剂（rhIL-1ra）的有效性后，对胎儿绵羊进行羊膜腔内（IA）注射大肠杆菌LPS，部分在注射LPS前先IA注射rhIL-1ra。早产羔羊在妊娠82%时分娩。
rhIL-1ra可减轻IA LPS诱导的肺部炎症，表现为肺中性粒细胞和单核细胞浸润减少、诱导型一氧化氮合酶表达降低、肺IL-6和IL-1β mRNA表达减少以及气道髓过氧化物酶浓度降低。rhIL-1ra可抑制IA LPS诱导的胎儿全身炎症，表现为血浆IL-8、蛋白质羰基含量降低、血液中性粒细胞增多以及肝脏中血清淀粉样蛋白A3 mRNA表达降低。rhIL-1ra还部分阻断了IA LPS对肺成熟的影响。因此，阻断羊膜腔内的IL-1信号可抑制LPS诱导的绒毛膜羊膜炎所引发的胎儿肺部及全身炎症和肺成熟。
IL-1在绒毛膜羊膜炎诱导的胎儿炎症反应发病机制中起核心作用。
